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BRIEF TITLE: STUDY OF THE SAFETY AND PHARMACOLOGY OF ATEZOLIZUMAB ADMINISTERED WITH OR WITHOUT BACILLE CALMETTE-GUÉRIN IN PATIENTS WITH HIGH-RISK NON-MUSCLE-INVASIVE BLADDER CANCER

A Phase Ib/II, Open-Label Study of the Safety and Pharmacology of Atezolizumab Administered With or Without Bacille Calmette-Guérin in Patients With High-Risk Non−Muscle-Invasive Bladder Cancer


  • Org Study ID: WO29635
  • Secondary ID:
  • NCT ID: NCT02792192
  • NCT Alias:
  • Sponsor: Hoffmann-La Roche - Industry
  • Source: Hoffmann-La Roche

Brief Summary

This Phase Ib/II study is designed to assess the safety, tolerability, pharmacokinetics, immunogenicity, patient reported outcomes (PROs), and preliminary anti-tumor activity of atezolizumab administered by intravenous (IV) infusion alone and in combination with intravesical BCG in high-risk NMIBC participants. The study will be conducted in following cohorts: Cohort 1A, Cohort 1B, Cohort 2, and Cohort 3. Atezolizumab will be administered at a fixed dose of 1200 milligrams (mg) every 3 weeks (q3w) for a maximum of 96 weeks. BCG will be administered to evaluate dose-limiting toxicities (DLTs), maximum tolerated dose (MTD), or maximum administered dose (MAD). De-escalation will be allowed for up to three dose levels of BCG (full dose [50 mg], 66 percent [%] of a full dose, and 33% of a full dose [Cohort 1B only]). After the MTD or MAD is determined for Cohort 1B, this dose will be used for all subsequent participants enrolled into Cohorts 1B, 2, and 3, unless the MTD is determined to be 33% of a full BCG dose. If MTD is determined to be 33% of a full BCG dose, then, no participants will be enrolled into Cohorts 2 and 3 until an assessment of the safety and activity of the combination of atezolizumab plus 33% of a full BCG dose is completed.

Overal Status Start Date Phase Study Type
Recruiting June 13, 2016 Phase 1/Phase 2 Interventional

Primary Outcomes:

Primary Outcome 1 - Measure: Percentage of Participants With Adverse Events

Primary Outcome 1 - Time Frame: From Baseline up to end of study (up to approximately 3.5 years)

Primary Outcome 2 - Measure: Cohort 1B: Percentage of Participants With DLTs of BCG

Primary Outcome 2 - Time Frame: Days 1-21

Primary Outcome 3 - Measure: Cohort 1B: MTD or MAD of BCG

Primary Outcome 3 - Time Frame: Days 1-21

Primary Outcome 4 - Measure: Percentage of Participants With Complete Response (CR) as Assessed by the Investigator on the Basis of Cystoscopy and Urine Cytology at Month 6

Primary Outcome 4 - Time Frame: 6 months

Condition:

  • Bladder Cancer

Eligibility

Criteria:
Inclusion Criteria:

- Histologically confirmed non-muscle-invasive transitional cell carcinoma (TCC) of the
bladder with carcinoma in-situ (CIS)

- High-risk NMIBC defined by the following:

BCG-unresponsive NMIBC:<br/>
Persistence of high-grade CIS at 6 months following an adequate course of BCG; or
Stage/grade progression at 3 months after induction BCG; or Recurrence of high-grade CIS
after achieving a disease-free state (i.e., CR) following induction of an adequate course
of BCG that occurs less than (<) 6 months after the last exposure to BCG

BCG-relapsing NMIBC:

Recurrence of high-grade CIS after achieving a disease-free state following induction of an
adequate course of BCG that occurs greater than or equal to (>/=) 6 months after the last
exposure to BCG

Very high-risk (VHR) BCG-naïve NMIBC:

VHR NMIBC, defined as having at least 1 of the following: Multiple and/or large (greater
than [>] 3 centimeters [cm]) T1, (HG/G3) tumors; T1, (HG/G3) tumor with concurrent CIS; T1,
G3 with CIS in prostatic urethra; Micropapillary variant of non-muscle invasive urothelial
carcinoma

- For BCG-unresponsive and BCG-relapsing NMIBC, participants must have received an
adequate course of BCG

- Resection of all pTa/pT1 papillary disease

- No prior radiation to bladder or pelvic region

- Eastern Cooperative Oncology Group (ECOG) performance status of less than or equal to
(
- Life expectancy >/=12 weeks

- Adequate hematologic and end-organ function

- Creatinine clearance >/=30 milliliters per minute (mL/min) (calculated using the
Cockcroft-Gault formula)

- For women of childbearing potential: agreement to remain abstinent (refrain from
heterosexual intercourse) or use contraceptive methods that result in a failure rate
of <1% per year during the treatment period and for at least 5 months after the last
dose of study drug

- For men receiving BCG: Agreement to remain abstinent (refrain from sexual intercourse)
or use a condom

- Tumor tissue biopsy within 60 days prior to study entry or availability of an archival
specimen obtained within 60 days of study screening

Exclusion Criteria:

- Evidence of locally advanced, metastatic, muscle-invasive, and/or extravesical bladder
cancer

- Any malignancy within 5 years prior to Cycle 1, Day 1

- History of autoimmune disease, idiopathic pulmonary fibrosis, organizing pneumonia
(e.g., bronchiolitis obliterans), drug-induced pneumonitis, idiopathic pneumonitis, or
active pneumonitis

- Signs or symptoms of infection within 2 weeks prior to the first dose of study
treatment

- Treatment with therapeutic oral or IV antibiotics within 2 weeks prior to the first
dose of study treatment

- Treatment with any approved anti-cancer therapy within 3 weeks prior to the first dose
of study treatment

- Treatment with any other investigational agent or participation in another clinical
trial with therapeutic intent within 4 weeks prior to the first dose of study
treatment

- Pregnant or lactating women, or women intending to become pregnant during the study

- Prior allogeneic stem cell or solid organ transplantation

- Positive test for human immunodeficiency virus (HIV)

- Active hepatitis B or C and/or tuberculosis

- Severe infections within 28 days prior to the first dose of study treatment

- Significant cardiovascular disease

- Major surgical procedure other than for diagnosis within 4 weeks prior to the first
dose of study treatment, or anticipation of need for a major surgical procedure during
the course of the study

- Administration of a live/attenuated vaccine within 4 weeks prior to the first dose of
study treatment, within 5 months following the administration of the last dose of
study drug, or anticipation that such a live/attenuated vaccine will be required
during the study

- History of prior significant toxicity or intolerance to BCG requiring discontinuation
of treatment

- History of prior systemic BCG infection

- History of immunosuppression, or conditions associated with congenital or acquired
immune deficiency

- Concurrent febrile illness, urinary tract infection, or gross hematuria

- Prior treatment with cluster of differentiation 137 (CD137) agonists or immune
checkpoint blockade therapies

- Treatment with systemic immunostimulatory agents within 6 weeks or five half-lives of
the drug, whichever is shorter, prior to the first dose of study treatment

- Treatment with systemic immunosuppressive medications within 2 weeks prior to the
first dose of study treatment, or anticipated requirement for systemic
immunosuppressive medications during the trial
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Gender: All

Minimum Age: 18 Years

Maximum Age: N/A

Healthy Volunteers: No

Official Information

Name: Clinical Trials

Role: Study Director

Affiliation: Hoffmann-La Roche

Overall Contact

Name: Reference Study ID Number: WO29635 www.roche.com/about_roche/roche_worldwide.htm

Phone: 888-662-6728 (U.S. and Canada)

Email: global-roche-genentech-trials@gene.com

Locations

Facility Status Contact
Urology Centers of Alabama
Homewood, Alabama 35209
United States
Recruiting
UCLA Urology Clark Clinic
Los Angeles, California 90095
United States
Recruiting
Stanford Univ.
Stanford, California 94305
United States
Recruiting
University of Chicago Medical Center
Chicago, Illinois 60637
United States
Recruiting
University of Iowa Hospitals & Clinics; Urology
Iowa City, Iowa 52242-5002
United States
Recruiting
Johns Hopkins Kimmel Cancer Center, Office of Research Administration
Baltimore, Maryland 21205
United States
Recruiting
Massachusetts General Hospital
Boston, Massachusetts 02114
United States
Recruiting
The Montefiore Medical Center & The Albert Einstein College of Medicine; Department of Urology
Bronx, New York 10461
United States
Recruiting
Memorial Sloan Kettering Cancer Center
New York, New York 10065
United States
Withdrawn
Duke University
Durham, North Carolina 27705
United States
Recruiting
Ohio State University
Columbus, Ohio 43210
United States
Recruiting
Oklahoma University Health Sciences Center
Oklahoma City, Oklahoma 73104
United States
Recruiting
VA Portland Healthcare System
Portland, Oregon 97239
United States
Recruiting
Carolina Urologic Research Center
Myrtle Beach, South Carolina 29572
United States
Active, not recruiting
Medical College of Wisconsin; Dept Froedtert Clin Can Ctr
Milwaukee, Wisconsin 53226
United States
Terminated